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Peripheral Vasodilation in Obese Humans

肥胖人群的外周血管舒张

基本信息

批准号：
8515512
负责人：
WILLIAM G SCHRAGE
金额：
$ 52.34万
依托单位：
UNIVERSITY OF WISCONSIN-MADISON
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-09-01 至 2016-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8515512
关键词：
Accounting Activities of Daily Living Acute Address Adult Age Aging Animal Model Ants Arteries Biological Availability Biopsy Blood Vessels Blood flow Body Weight decreased Cardiovascular Diseases Chronic Clinical Data Detection Development Diabetes Mellitus Disease Disease Progression Doppler Ultrasound Drug Delivery Systems Elderly Endothelial Cells Endothelium Environment Enzymes Epidemic Event Exercise Exercise Tolerance Exhibits Functional disorder Goals Health Health Care Costs Human Hyperglycemia Hypertension Impairment Infusion procedures Insulin Resistance Intervention Limb structure Link Measures Mechanics Mediating Metabolic Metabolic Diseases Metabolic syndrome Microcirculation Molecular Muscle Nitric Oxide Obesity Obesity associated disease Obstructive Sleep Apnea Oxidants Pathway interactions Patients Peripheral Peripheral Resistance Pharmaceutical Preparations Phenotype Physical activity Physiological Physiology Play Process Prophylactic treatment Prostaglandins Protocols documentation Public Health Quality of life Rattus Reactive Oxygen Species Recovery Regulation Research Rest Risk Role Sampling Signal Transduction Skeletal Muscle Staging Testing Time Vasoconstrictor Agents Vasodilation Vasodilator Agents age effect base cardiovascular risk factor combat constriction design diet and exercise disease diagnosis emerging adult glucose uptake improved improved functioning novel novel therapeutics pre-clinical premature programs relating to nervous system response restoration therapeutic target vasoconstriction young adult

项目摘要

DESCRIPTION (provided by applicant): The overall goal of this research program is to investigate the obesity-related changes in microvascular function that initiate the cardiovascular disease process. The growing population of obese adults is predicted to create a large public health burden in the next few decades. Skeletal muscle accounts for the majority of peripheral resistance and glucose uptake in humans. Decreased muscle vasodilation likely contributes to hypertension and sets the stage for hyperglycemia-both hallmarks of metabolic syndrome and diabetes. Thus, low muscle blood flow in obese humans may contribute to reduced exercise capacity-this in turn sets the stage for development of long-term cardiovascular diseases like diabetes. We propose to study younger obese "metabolically health" adults (18-35 yrs), without confounding effects of age, metabolic syndrome, or diabetes- before the negative effects of obesity can exert their full negative impact. The general hypothesis is that obesity impairs endothelium dependent dilation (EDD) and exercise vasodilation via increased reactive oxygen species (ROS) and reductions in vasodilator signals and increased vasoconstrictor signals. Our preliminary data suggest young obese adults exhibit reduced EDD and exercise vasodilation, and acute ROS scavenging improves both. We will test our hypotheses by arterial drug infusion to test EDD mechanisms in lean and obese humans. We will use similar approaches to test vascular mechanisms controlling blood flow during dynamic exercise. Next, we will test EDD and exercise vascular responses before and after a diet and exercise intervention, where we can parcel out whether physical activity or weight loss plays a larger role in vascular improvements. Finally, we will sample artery endothelial cells from these same subjects to identify molecular pathways that change with obesity as potential therapeutic targets. These studies integrate physiologic, pharmacologic, and molecular approaches to test our hypotheses. We have several exciting preliminary findings that support our hypotheses, and have designed a complementary set of Aims the will soundly address our research questions. A multi-disciplinary, state-of-the-art approach will be used to pursue these aims, which will provide fundamental mechanistic understanding of EDD and exercise mechanisms responsible for reduced blood flow in obese humans. Our novel findings will guide the development of novel therapeutic strategies for obesity and other diseases, including obstructive sleep apnea, metabolic syndrome and diabetes.

描述（由申请人提供）：